The peripheral GABAergic system as a target in endocrine disorders

Gladkevich, Anatoliy V.; Korf, Jakob; Hakobyan, V.P.; Melkonyan, K.V.

doi:10.1016/j.autneu.2005.11.002

Cited by 116 publications

(99 citation statements)

References 82 publications

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“…The endogenous ligand for GABA B receptors, GABA, has also been identified in many peripheral tissues, especially in endocrine organs such as the pituitary, pancreas, testis, gastrointestinal tract, ovary, placenta, uterus, and adrenal medulla (10). Peripheral GABA has been suggested to act not only as a neurotransmitter or neuromodulator in the autonomic nervous system but also as a hormone or trophic factor in nonneuronal tissue (19).…”

Section: Discussionmentioning

confidence: 99%

Functional expression of the GABA_B receptor in human airway smooth muscle

Osawa¹,

Xu²,

Sternberg³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian central nervous system and exerts its actions via both ionotropic (GABAA/GABAC) and metabotropic (GABAB) receptors (R). In addition to their location on neurons, GABA and functional GABAB receptors have been detected in nonneuronal cells in peripheral tissue. Although the GABABR has been shown to function as a prejunctional inhibitory receptor on parasympathetic nerves in the lung, the expression and functional coupling of GABAB receptors to Gi in airway smooth muscle itself have never been described. We detected the mRNA encoding multiple-splice variants of the GABABR1 and GABABR2 in total RNA isolated from native human and guinea pig airway smooth muscle and from RNA isolated from cultured human airway smooth muscle (HASM) cells. Immunoblots identified the GABABR1 and GABABR2 proteins in human native and cultured airway smooth muscle. The GABABR1 protein was immunohistochemically localized to airway smooth muscle in guinea pig tracheal rings. Baclofen, a GABABR agonist, elicited a concentration-dependent stimulation of [35S]GTPγS binding in HASM homogenates that was abrogated by the GABABR antagonist CGP-35348. Baclofen also inhibited adenylyl cyclase activity and induced ERK phosphorylation in HASM. Another GABABR agonist, SKF-97541, mimicked while pertussis toxin blocked baclofen’s effect on ERK phosphorylation, implicating Gi protein coupling. Functional GABAB receptors are expressed in HASM. GABA may modulate an uncharacterized signaling cascade via GABAB receptors coupled to the Gi protein in airway smooth muscle.

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Section: Discussionmentioning

confidence: 99%

Functional expression of the GABA_B receptor in human airway smooth muscle

Osawa¹,

Xu²,

Sternberg³

et al. 2006

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…It is known that GABA is an inhibitory neurotransmitter in the central nervous system, and participates in most of the inhibitory synapses that enable neuronal activity. In spite of this, this compound has also been also described in a variety of cellular events in non-neuronal peripheral tissues, which has led some authors to suggest it is a trophic factor, or even a hormone (Ong and Kerr, 1990;Gladkevich et al, 2006). GABA is also present in tissues such as the human uterus, oviducts and ovaries (Erdö et al, 1989), as well as in certain fl uids, such as human seminal plasma (Leader et al, 1992).…”

Section: Gamma-aminobutyric Acidmentioning

confidence: 99%

Modulation of spermatozoon acrosome reaction

Vigil¹,

Orellana²,

Cortés³

2011

Biol. Res.

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Spermatozoon acrosome reaction is an exocytotic event of the utmost importance for the development of mammalian fertilisation. Current evidence shows that the triggering of the acrosome reaction (AR) could be regulated by the action of diverse compounds, namely, metabolites, neurotransmitters and hormones. The aim of the present review is to describe the modulating effects of several compounds that have been classifi ed as inductors or inhibitors of acrosome reaction. Among AR inductors, it is necessary to mention progesterone, angiotensin II, atrial natriuretic peptide, cathecolamines, insulin, leptin, relaxin and other hormones. Regarding the inhibitors, oestradiol and epidermal growth factor are among the substances that retard AR. It is worth mentioning that gamma-aminobutyric acid, a neurotransmitter known to be an inhibitor in the central nervous system, has been shown to induce AR. The multiple hormones located in the fl uids of the female reproductive tract are also likely to act as subtle regulators of AR, constituting a fundamental aspect for the development of successful fertilisation. Finally, it is necessary to emphasise that the study of regulation exerted by hormones and other compounds on AR is essential for further understanding of mammalian reproductive biology, especially spermatozoon physiology.

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“…Outside the nervous system GABA is produced by the pancreatic islet  cells and is present in blood in low concentrations. Pancreatic  cells and some blood cells express GABA A channels (Gladkevich et al, 2006;Olsen and Sieghart, 2008). In T lymphocytes it is known that neurotransmitters´ receptors can be regulated by the T cell receptor activation, cytokines or the neurotransmitters themselves (Bjurstom et al, 2008; have in normal T cell function and disease.…”

Section: Introductionmentioning

confidence: 99%